http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
- 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
- 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
RISS 인기검색어
- 검색키워드
- 주제어 : Trametinib (검색결과 5 건)
- 무료
- 기관 내 무료
- 유료
-
( Donghwi Jang ),( Jongeun Lee ),( Jaihee Bae ),( Yeonjoo Jung ),( Heeyeon Kim ),( Se Jin Oh ),( Jong Hee Lee ),( Dong-youn Lee ),( Ji-hye Park ) 대한피부과학회 2023 대한피부과학회지 Vol.61 No.1
Bullous pemphigoid (BP) is a chronic and recurrent bullous disorder that may be associated with the administration of certain drugs. Recently, bullous cutaneous adverse events after immunotherapy (IT) or targeted therapy have been increasingly reported. Here, we report a case of BP in a patient diagnosed with metastatic melanoma after treatment with pembrolizumab, dabrafenib, and trametinib. Histopathological examination showed a subepidermal blister with perivascular lymphocytic and eosinophilic infiltration; the accompanying findings of linear immunoglobulin G and C3 deposition by immunofluorescence microscopy were consistent with BP. Since IT agents may initiate immune dysregulation and pathologic autoantibody production, which are required for the pathogenesis of BP, the lesions were thought to be cutaneous adverse events caused by IT. (Korean J Dermatol 2023;61(1):62∼65)
-
Combination effect of trametinib and BC-LI-0186 inhibitor in non-small cell lung cancer
( Sang Hoon Lee ),( Eun Young Kim ),( Arum Kim ),( Kim Taehee ),( Yoon Soo Chang ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
Objective: Although KRAS mutation is most common mutation in non-small cell lung cancer, there are no proven therapeutic agents up to date. Trametinib is FDA-approved agent for melanoma, which showed anti-cancer effect through MEK 1/2 signal pathway. And we reported the effect of 3rd generation of mTOR inhibitor, BCLI- 0186, in non-small cell lung cancer (NSCLC) in previous study. In this study, we investigated the combination effect of two drug in NSCLC. Methods: Cell line (A549 cell and H460 cell) growth inhibition effect with drug combination in vitro was analyzed by obtaining combination index, suggested by Chou-Talalay. Anti-tumor effect of trametinib and BC-LI-0186 was evaluated with immunohistochemical staining, immunoblotting, and CT image. A total of 117 patients with NSCLC were analyzed by immunohistochemistry, and RNA sequencing was done in Macrogen. Results: Firstly, we confirmed the Leucyl-tRNA synthetase (LRS) was overexpressed (44.5% of patients showed strong expression) and positive correlation between LRS and mTORC1 marker including pS6 in NSCLC tissue. Genetic ablation of LRS showed decreased expression of pS6. Chemical inhibitor, BC-LI-0186 showed same pattern. However, in full growth media status, BC-LI-0186 failed to inhibit the pS6. Therefore, we could predict that there was a bypass, and through RNA sequencing, the MEK path was estimated as one of the bypasses. Combination of Trametinib 30nM and BC-LI-0186 2μM showed synergic effect in inhibition of phosphorylation of S6, MEK, and ERK in H460 cell and H1299 cell lines. Conclusions: The pathway to evade the effect of BC-LI-0186 inhibitor is assumed to be one of the pathways of MEK, and the combination with trametinib may be effective in NSCLC. Our study showed a new therapeutic strategy for NSCLC with KRAS activating mutation
-
Eunjeong Ko,Seungjae Baek,Jiwon Kim,Deokbae Park,이영기 한국발생생물학회 2020 발생과 생식 Vol.24 No.2
Metformin has been widely used as an antidiabetic drug, and reported to inhibit cell proliferation in many cancers including non-small cell lung cancer (NSCLC). In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure. Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. The present study tested the combination therapy of metformin and trametinib by monitoring the alterations of regulatory effector proteins of cell signaling pathways and the effect of the combination on cell viability in NCI-H2087 NSCLC cells with NRAS and BRAF mutations. We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK. The combination therapy synergistically decreased cell viability in treatment with low doses of two drugs, while it gave antagonistic effect with high doses. These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific celular context of cancer cells.
-
이상훈,김은영,한정민,한균희,장윤수 대한암학회 2023 Cancer Research and Treatment Vol.55 No.3
Purpose The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC). Materials and Methods Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model. Results LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model. Conclusion The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.
-
Elona Malja 대한핵의학회 2024 핵의학 분자영상 Vol.58 No.2
Redifferentiation therapy with Dabrafenib (a BRAF inhibitor) and Trametinib (a MEK inhibitor) restores radioiodine avidityof radioiodine-refractory papillary thyroid carcinoma (PTC). A 50-year-old man was diagnosed with radioiodine-refractoryPTC pulmonary metastasis post prior total thyroidectomy and radioiodine ablation. The patient was treated with Dabrafeniband Trametinib, followed by second radioiodine ablation with I-131 sodium iodine. Diffuse increased radioiodine uptakeby pulmonary metastasis was visualized on post ablation whole body scan. Response to second radioiodine ablation wasdemonstrated by decrease in size of pulmonary nodules seen on chest CT, along with decrease of thyroglobulin level.
ScienceON연관 검색어 추천
이 검색어로 많이 본 자료
활용도 높은 자료
